The purpose of this research is to develop an in vitro assay system for detection of genetic predisposition for cancer of the colon and rectum. Cell cultures from skin and colonic mucosa biopsies will be established from patients with colonic cancer with and without polyposis, their relatives at-risk and family members by-marriage and non-family members without a family cancer history as controls. The influence of cancer-prone germinal mutations on the in vitro biological features (morphology, growth parameters, mitosis, surface topography and epithelial-specific enzyme activities) of cultures derived from these 4 groups will be evaluated. Somatic mutations (spontaneous and induced by either the mutagen ethylmethane-sulfonate or ultraviolet light will be studied using the in vitro markers for 2 mutants, resistance to ouabain and ability to use fructose. Transformation, defined as the acquisition of a biological property not present in the parent culture, (spontaneous and induced by either the carcinogen urethane or MNNG) will be studied by a panel of 11 properties considered to be criteria of transformation. The aims of this in vitro research on colorectal cancer is to (1) delineate the biological properties of cancer of the colon and rectum and (2) to develop an assay to identify individual genetic risk of colorectal cancer.